Abnormalities of the vas deferens and epididymis in cryptorchid boys with congenital rubella.

Cryptorchidism was present in 12% of 316 boys with congenital rubella (CR) followed by The Roosevelt Hospital Rubella Project. Eight of these patients, age 4 through 16 yr, had a recent orchiopexy, 4 on the left, 2 on the right, and 2 bilaterally. The vasoepididymal system was absent or apparently obstructed in 60% of the 10 sides. The epididymis was abnormal in 6 instances and the vas deferens in 5. Sixty-one boys of the entire series had an intravenous pyelogram (IVP) that was significantly abnormal in 18%. The 8 patients described all had a normal IVP except for 2 who had a malrotated kidney on the involved side. In 5 of the 8, a known maternal rubella infection has occurred during the first 8 wk of gestation. As the rubella virus is known to interfere with cellular growth and tissue differentiation in early pregnancy, it apparently altered the developing testis and mesonephric duct system. Similar vasoepididymal abnormalities have been described previously in patients with uncomplicated cryptorchidism, inguinal hernia, kidney defects, cystic fibrosis and male sterility. Their presence should alert the clinician to perform an IVP and also consider a diagnosis of congenital rubella.     

Acquisition of androgen-mediated expression of mouse vas deferens protein (MVDP) gene in cultured epithelial cells and in vas deferens during postnatal development

We used cultured vas deferens epithelial cells (VDECs) as a model system to determine the conditions that allow mouse vas deferens protein (MVDP) gene expression and acquisition of androgen responsiveness. On the basis of Northern blot analysis, the mvdp gene is constitutively expressed at very low levels in prepubertal VDECs grown on collagen-coated plastic or on microporous membrane inserts. In the presence of dihydrotestosterone (DHT), mvdp messenger RNA levels dramatically increased in cells cultured on microporous membrane inserts and stayed unchanged in cells grown on matrix-coated plastic. Epithelial cells derived from fetal vas deferens were able to synthesize MVDP in response to DHT, and the presence of fetal mesenchymal cells did not influence MVDP production. Providing the cells with a culture procedure that permits access to the basolateral membranes and caters to the polarity requirements of the cell is a prerequisite for androgen induction of MVDP gene expression. The results also point to a role for epidermal growth factor, insulin, and tyrosine kinase activity in mediating the action of androgen on mvdp gene expression. In vivo studies show that the first expression of the mvdp gene between 5 and 7 days postpartum is not associated with major structural changes in the epithelium. The acquisition of a mature phenotype by epithelial and peritubular contractile cells, between 10 and 20 days, correlates with androgen dependency of the mvdp gene. We propose that cell differentiation and polarization on a matrix-coated microporous membrane reproduces some of the events that are necessary for acquisition of androgenic responsiveness of the mvdp gene during postnatal development.     

Cell- and region-specific localization of lysosomal and secretory proteins and endocytic receptors in epithelial cells of the cauda epididymidis and vas deferens of the adult rat.

The epithelial cells lining the cauda epididymidis and vas deferens are active in endocytosis and have an abundance of lysosomes and a well-characterized secretory apparatus. However, little is known about the nature of lysosomal proteins contained within lysosomes, the types of receptors on the cell surface, and the types of proteins secreted by these cells. In the present study, cathepsins A, D, B, and sulfated glycoprotein (SGP)-1, well-characterized lysosomal proteins, as well as SGP-2, a secretory protein and low-density lipoprotein receptor-related protein-2 (LRP-2), an endocytic receptor, were immunolocalized at the light-microscopic level within epithelial cells of the cauda epididymidis and vas deferens. Principal cells showed numerous intensely reactive lysosomes for cathepsins A, D, and SGP-1 in all regions of the cauda and vas deferens and for cathepsin B only in the cauda epididymidis. Basal cells were intensely reactive for cathepsin A, unreactive for cathepsins D and B, and weakly reactive for SGP-1 in the cauda region. In the vas deferens, these cells were intensely reactive for cathepsin A and SGP-1 and unreactive for cathepsin B; in the case of cathepsin D, basal cells were weakly reactive in the proximal vas deferens but intensely reactive in the middle and distal vas deferens. Clear cells, present in the cauda region and proximal vas deferens, were intensely reactive for cathepsin A, weakly reactive for SGP-1, and unreactive for cathepsins D and B, while narrow cells found mainly in the proximal vas deferens were intensely reactive for cathepsins A, D, and SGP-1 and unreactive for cathepsin B. Thus, the expression of different lysosomal enzymes in the cauda epididymidis and vas deferens is not only cell- but also region-specific, suggesting differences in the type of substrates internalized by these cells. SGP-2, a secretory protein, showed a checkerboardlike staining pattern in the cytoplasm of principal cells of the cauda epididymidis, while the cytoplasm of all principal cells were intensely reactive in the vas deferens. This type of reaction, as well as staining of sperm, suggests that SGP-2 is secreted into the lumen, where it functions in relation to sperm. The endocytic receptor LRP-2 was noted only on the apical surface of principal cells of the cauda and vas deferens and in spherical structures indicative of endosomes suggestive of their role in the uptake of various ligands, including SGP-2, for which it has a high binding affinity. Thus SGP-2 in the cauda and vas deferens is not only secreted but endocytosed by principal cells, suggestive of an active turnover in the lumen. In summary, the epithelial cells of the cauda and vas deferens show marked differences in expression of lysosomal proteins, SGP-2, and LRP-2 suggestive of differences in their functional activity while sperm are stored and protected in these regions.     

Structural features of cultured epithelial cells from the adult rat epididymis

Epithelial cells isolated from the caput epididymidis of adult rats were placed in primary culture and examined daily for ten days for changes in external anatomy, reorganization of cytoskeletal components, maintenance of characteristic cytoplasmic features, and response to media formulated to minimize nonepithelial cell proliferation. Significant cell attachment to the substrate began after the first 24 hours of culture. After attachment, the cells underwent a progressive flattening and became closely applied to the substrate. This was accompanied by a redistribution of microvilli on the cell surface and a reorganization of cytoskeletal elements within the cell. After flattening, the cultured cells displayed an extensive array of 10-nm filaments which were associated with the desmosomes attaching adjacent cells. Immunofluorescence studies demonstrated that these were keratin-containing intermediate filaments and 2-D gel electrophoresis of intact cells and cell cytoskeletons revealed that a family of "keratin-like" polypeptides were major components of the cells. Epithelial cell attachment, morphology, and maintenance in the primary culture were unaffected by D-valine, cytosine arabinoside, or both; however, these agents, either individually or in combination, reduced significantly the number of cells incorporating 3H-thymidine. These data show that isolated epithelial cells retain some differentiated structural features that characterize the intact cell and that enriched cultures of epithelial cells can be maintained under conditions where fibroblast proliferation is inhibited.     

Glandular inclusions in inguinal hernia sacs: morphologic and immunohistochemical distinction from epididymis and vas deferens

Glandular inclusions in inguinal hernia sacs may bear a striking resemblance to the epididymis or vas deferens. Misinterpretation as a transected functional structure may raise significant concerns regarding reproductive capability, even if encountered unilaterally. In a child, resolution of these concerns may be years away with the onset of puberty and documentation of normal sperm counts. CD10 has been shown to be present in Wolffian-type epithelium and to be absent in Mullerian-type epithelium. We hypothesized that an antibody to CD10 would react with vas deferens and epididymis and fail to react with hernia sac inclusions, most of which we thought were Mullerian duct-derived structures. Glandular inclusions in 29 hernia sacs from prepubertal males were classified histologically according to their resemblance to normal structures and analyzed for CD10 by immunohistochemistry. Inclusions resembling vas deferens had their external diameters measured and were also stained for smooth muscle actin. Thirty-one examples of normal vas deferens and 13 examples of normal epididymis were included for comparison. The inclusions were classified as vas deferens-like (9), epididymis-like (13), and Mullerian-like (7). CD10 reactivity was lacking in all vas deferens-like inclusions; their median external diameter was 0.6 mm. Of the epididymis-like inclusions, 7 of 13 were CD10 positive. The CD10-negative cases consisted of glands with well-defined stromal coats distinct from adjacent stromal coats. CD10-positive cases were more numerous, more tightly aggregated, and surrounded by less well-developed stromal coats that blended with adjacent coats. All seven Mullerian-like remnants were CD10 negative. All normal vas deferens and epididymis showed at least focal CD10 reactivity. CD10 positivity in all cases had a luminal membranous staining pattern. Both the vas deferens-like inclusions and the normal vas deferens showed strong smooth muscle actin positivity in their stromal coats. CD10 negativity and external diameter <1 mm are highly useful to distinguish vas deferens-like inclusions from true vas deferens. Epididymis-like inclusions are more problematic. Some react for CD10 and may represent aberrant Wolffian ductules. Others are CD10 negative, distinct from true epididymis, and may be of Mullerian differentiation. Mullerian-like remnants can be diagnosed on the basis of their limited number and scattered distribution. Lack of CD10 immunostaining corroborates this interpretation.     

Reconstruction of vas deferens

If the vas deferens repair operation is done in properly selected pa tients, it is possible to achieve success in 50% of cases. The method o f reconstruction used by the author is outlined and technical difficulti es are indicated. The longer the time interval between vasectomy and the repair operation, the less the chances of success. Where the interval is more than 5 years, a preliminary testicular biopsy is advised. It is better to limit the operation to patients below the age of 45 years. Care must be taken to avoid injury to blood vessels. End- to-end union of cut ends without tension must be made over an indwelling splint. The splint is removed after 6 days. When sufficient length of the vas is not available for repair without tension, a mobilization of the vas may be done similar to what is done in cases of undescended testicle. When the distal end of the vas is too short or stenosed, a vasoepididymal anastomosis may be possible. Placing a splint in these cases has been advocated also. It is better to do the operation on 1 side only. If spermatozoa are absent after 3 months, the other side may then be operated on.     

5α-还原酶I型同功酶基因在人睾丸、附睾和输精管组织中的表达

我们对人５α－还原酶Ｉ型同功酶基因在正常人睾丸、附睾及输精管组织细胞内的定位表达进行了初步的研究。采用非同位素地高辛标记ｃＲＮＡ探针对人睾丸、附睾和输精管组织冰冻切片进行原位杂交。结果：人睾丸Ｓｅｒｔｏｌｉ和Ｌｅｙｄｉｇ细胞胞浆、附睾和输精管上皮的主细胞及假复层柱状上皮细胞的胞浆中均有较强的杂交信号；细胞核中未见杂交信号；睾丸生精细胞及基底膜、附睾和输精管上皮的基底膜、间质和肌层也未见杂交信号。证明人与灵长类和大鼠的５α－还原酶基因表达及其分布基本一致。本结果对深入研究５α－还原酶及其产物在人类生殖中的作用具重要意义。     

Principal cells of the vas deferens are involved in water transport and steroid synthesis in the adult rat

Principal cells show marked structural differences in the proximal, middle, and distal regions of the vas deferens, reflective of diverse functional activities. In the present study, we performed electron microscopy to examine the structural features of principal cells using glutaraldehyde-fixed, Epon-embedded material, while functional parameters were examined using light microscopic immunocytochemistry on Bouin-fixed, paraffin-embedded material. In the proximal region, the cuboidal principal cells resembled those of the cauda epididymidis, but few clear cells and occasional narrow cells were present. In the middle region, principal cells often contained blebs of their apical cytoplasm containing vesicular and tubular profiles. These blebs extended far from the cell surface and appeared to be liberated into the lumen, suggesting an apocrine type of secretion. In the distal region, dilated intercellular spaces containing numerous membranous profiles of different shapes and sizes were noted between adjacent principal cells and overlying basal cells. The use of an anti-aquaporin-1 antibody revealed an intense reaction over the endothelial cells of numerous vascular channels in the lamina propria. Taken together, these observations suggested water transport from the lumen of the vas deferens via the dilated spaces to underlying vascular channels, the function of which may be to concentrate sperm. The infranuclear cytoplasm of principal cells of this region showed whorls of smooth endoplasmic reticulum (sER). Large intracytoplasmic cavities were found within the sER aggregates, and these contained membranous profiles that appeared to peel off from the surrounding sER elements. Various images of such cavities closely juxtaposed to the lateral plasma membrane suggested that the membranous profiles of the intercellular spaces were derived from them. Use of anti-3beta-hydroxysteroid dehydrogenase antibody revealed an intense reaction over principal cells of the vas deferens, as well as over the blebs in the lumen of the vas deferens, which is indicative of the steroid synthesis performed by these cells. The release of sER membranous profiles into the dilated spaces and the presence of blebs in the lumen may represent a means of transporting steroids that are destined for different sites out of the principal cells. Steroids in the blebs would be ultimately destined for utilization by luminal sperm, while those steroids in the dilated spaces are designed for utilization by muscle layers of the lamina propria. In summary, principal cells of the vas deferens appear to be involved in synthesis and secretion of steroids and in eliminating water from the lumen of the vas deferens.     

Testosterone and dihydrotestosterone levels in the epididymis, vas deferens and preputial gland of mice during sexual maturation

The levels of testosterone (T) and dihydrotestosterone (DHT) in the epididymis, vas deferens and preputial gland were assessed in mice from 1 to 90 days. The weight increase of these 3 organs was proportionately greater than that of the whole body until 50 or 60 days, and they attained their adult histological appearance approximately 20 days prior to puberty. Expressed in ng/g, the concentration of androgens (T+DHT) in the epididymis (14.3 to 36.5), vas deferens (6.6 to 24.0) and preputial gland (1.5 to 4.7) were higher than in plasma (0.2 to 3.6 ng/ml). The concentration of either androgen varied little during sexual maturation and was not correlated with circulating levels. The highest concentration of androgen (T+DHT) was observed at birth suggesting that the neonatal period is crucial for development of the accessory sexual organs. In the epididymis and preputial gland T was the predominant androgen during the infantile phase of development, whilst DHT predominated thereafter. In the vas deferens concentrations of T were always equal to or higher than those of DHT. These results suggest that the ability of the accessory sexual organs to accumulate androgens appears to be more important than the circulating concentration of androgens in determining their growth and differentiation.     

Unilateral renal agenesia associated with partial epididymis and vas deferens agenesia in a patient with abdominal testicle

This study considers a unilateral renal agenesia associated with agenesia of the epididymis body and tail and the vas deferens and non-palpable left testicle in a 20-month-year-old patient. During laparoscopic procedure, the testicle was positioned at approximately 5 cm above the inguinal ring. The size was appropriate for the age and the head of the epididymis was situated in its normal position. The decision was made to perform the first step of the Fowler-Stephens' surgery and the patient presented a good evolution. The association of male duct system agenesia with unilateral renal agenesia in a patient with cryptorchidism diagnosed by laparoscopy is an extremely rare event, however generally in these cases the testicle is of normal size, presents unaltered hormonal function, and must be preserved.     

Congenital absence of the vas deferens.

Fourteen personal cases of agenesia of the vas deferens, bilateral in 12 and unilateral in 2, are described. In 13 of the cases the diagnosis was confirmed by surgical exploration. In most of the cases cytologic examination of aspiration biopsy specimens and histologic examination of surgical specimens of the testes showed that spermatogenesis was normal. The appearance of biopsy specimens of the epididymides were normal except for a certain degree of interstitital fibrosis and dilation of the ductus epididymidis. Endeavours to produce an artificial spermatocele with the aid of an isolated flap of tunica vaginalis in several patients proved unsuccessful. In one patient with a naturally preformed spermatocele the latter was aspirated, and the patient's wife was inseminated with the cellular content from the aspirate. This procedure has been repeated on several occasions, but so far without any subsequent conception. The failure of treatment of these patients may perhaps be due to some change in the function of their epididymides. This possibility is discussed.     

Cutaneous fistulas to the vas deferens.

Cutaneous fistulas to the vas deferens are a rare occurrence. A careful review of the literature revealed only 16 cases reported within the last 70 years. We present a case of such a fistula occurring after inguinal orchiectomy for suppurative epididymo-orchitis and review the etiologies of all reported cases to provide recommendations for management.     

Identification and characterization of an antigen recognized by monoclonal antibody TRA 54 in mouse epididymis and vas deferens

Spermatozoa in testicular fluid are known to have weak forward motility and cannot fertilize eggs. The epididymis is known to participate in sperm maturation leading fertilization, but little is known about the specific epididymal molecules involved in the modification of sperm. In this study, we characterized the new pattern of expression of an antigen previously identified in testicular germ cells by monoclonal antibody (mAb) TRA 54. This antigen is expressed in epididymal and vas deferens epithelial cells in mice older than 24 days but not during younger developmental stages. Evaluation by immunohistochemistry shows that antigen expression is limited to the cytoplasm of a specific cell population of epithelia along the epididymal regions and vas deferens of adult mice. The molecules synthesized and released by epididymal and vas deferens epithelia into their lumen seem to bind on spermatozoa moving down through the ducts. Immunoblot analysis showed that the molecules recognized by mAb TRA 54 in testis and epididymis were similar and share a common epitope involving carbohydrate domains. Interestingly, the antigens identified in epididymal and vas deferens epithelial cells were expressed independently of testicular germ cells and are produced in an androgen-dependent manner. Finally, the molecules recognized by mAb TRA 54 seem to play an important role in spermatogenesis, as well as in epididymal function related to spermatozoa maturation and ability to fertilize.     

The maturation of sperm motility in the epididymis and vas deferens of the vervet monkey, Cercopithecus aethiops

Among the diverse facets of sperm maturation, changes in motility are conspicuous and hence studies of sperm kinematics might provide good indices for sperm maturation. Accordingly, the maturation of sperm motility in the epididymis and vas deferens of the vervet monkey, Cercopithecus aethiops, was assessed using a computer-aided sperm motility analysis system. The results revealed clear trends in the development of both sperm motility per se and in the movement characteristics of motile spermatozoa from different regions of the epididymis, the vas deferens and the ejaculate, reflecting maturational changes associated with the attainment of functional motility and fertility. Motion of spermatozoa from the caput epididymis was sluggish and irregular. As the spermatozoa moved through the corpus epididymis, motility increased sharply, and continued to improve through the cauda epididymis and vas deferens. Despite the high proportion of motile cells, full maturation of motion capabilities was not completed in spermatozoa from the corpus epididymis. Only once spermatozoa had reached the cauda epididymis and vas deferens did they attain their full vigour, and swam rapidly (greater VCL, VSL and VAP) with straightline trajectories (greater LIN, WOB and STR; lower ALH, MAD and CURV). After acquiring their maximal percentage motility and progressive velocity in the cauda epididymis and vas deferens, a slight decline in motility and vigour occurred in ejaculated spermatozoa, and was possibly associated with the ageing of stored spermatozoa. The results from this investigation have revealed clear trends in the maturation of the motility of vervet monkey spermatozoa during their transit through the epididymis and vas deferens and final emergence in the ejaculate, and have provided crucial baseline information on the reproductive physiology of this potentially valuable biomedical model to serve as a reference for future studies in reproductive toxicology.     

Ectopia of the vas deferens

Ectopic location of the vas deferens is a rare congenital abnormality that has a spectrum of presentations. Such cases have been associated with anorectal anomalies. Knowledge of distal Wolffian duct embryology may help to explain the developmental steps involved in these anomalies, as well as provide theories for the variations that may be encountered. Vas deferens development is reviewed, and two cases of vas ectopia are presented to illustrate and lend support to current theories of normal and abnormal vasal embryology.